Abstract
The study aims to investigate the role of viscoelastic interactions between cells and extracellular matrix (ECM) in avascular tumor growth. Computer simulations of glioma multicellular tumor spheroid (MTS) growth are being carried out for various conditions. The calculations are based on a continuous model, which simulates oxygen transport into MTS; transitions between three cell phenotypes, cell transport, conditioned by hydrostatic forces in cell–ECM composite system, cell motility and cell adhesion. Visco-elastic cell aggregation and elastic ECM scaffold represent two compressible constituents of the composite. Cell–ECM interactions form a Transition Layer on the spheroid surface, where mechanical characteristics of tumor undergo rapid transition. This layer facilitates tumor progression to a great extent. The study demonstrates strong effects of ECM stiffness, mechanical deformations of the matrix and cell–cell adhesion on tumor progression. The simulations show in particular that at certain, rather high degrees of matrix stiffness a formation of distant multicellular clusters takes place, while at further increase of ECM stiffness subtumors do not form. The model also illustrates to what extent mere mechanical properties of cell–ECM system may contribute into variations of glioma invasion scenarios.
Highlights
Glioblastoma multiform (GBM) is one of the most lethal types of human cancers with a median survival time slightly above a year [1]
Experimental results for glioma multicellular tumor spheroid (MTS) [70] show the inner quasi-stationary cell density in dynamically growing spheroid about Ceq = 4 × 105 cells/mm3, which agrees well with their assessment of Ceq based on the volume VC = 1200 μm3 of EMT6/Ro tumor cells
Lower equilibrium volume fraction of 0.39 for tumor cells was taken in Ref. [69] for a model of GBM growth, which corresponds to Ceq = 3.2 × 105 cells/mm3
Summary
Glioblastoma multiform (GBM) is one of the most lethal types of human cancers with a median survival time slightly above a year [1]. Rapid proliferation and aggressive invasion into surrounding normal tissue is a hallmark of GBM This ability of long range infiltration of the primary tumor cells through brain tissue even in the absence of distant metastases, makes GBM a primary target of many research projects including in vitro studies and computer models [1,2,3]. It has been found [4, 5] that purely mechanical characteristics of glioma microenvironment may play pivotal role in the invasion process. There are number of observable trends reported by different authors [3, 7,8,9]
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